Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sci Immunol. 2022 Jul 15;7(73):eabg3208. doi: 10.1126/sciimmunol.abg3208. Epub 2022 Jul 8.
Despite being the most abundantly secreted immunoglobulin isotype, the pattern of reactivity of immunoglobulin A (IgA) antibodies toward each individual's own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found that the binding specificity of bulk fecal and serum IgA toward resident gut bacteria resolves well at the species level and has modest strain-level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, whereas a small portion displayed cross-reactivity. Orally administered hybridoma-produced IgAs still retained bacterial antigen binding capability, implying the potential for a new class of therapeutic antibodies. Species-specific IgAs had a range of strain specificities. Given the distinctive bacterial species and strain composition found in each individual's gut, our findings suggest the IgA antibody repertoire is shaped uniquely to bind "self" gut bacteria.
尽管免疫球蛋白 A（IgA）是分泌量最丰富的免疫球蛋白亚型，但针对每个人自身肠道共生菌的 IgA 抗体的反应模式仍然难以捉摸。通过用特定的共生菌定植无菌小鼠，我们发现大量粪便和血清 IgA 对常驻肠道细菌的结合特异性在物种水平上很好地解决了问题，并且具有适度的菌株特异性。从无菌小鼠的黏膜固有层 B 细胞中产生的 IgA 杂交瘤表明，大多数 IgA 克隆识别单个细菌物种，而一小部分显示交叉反应性。口服给予杂交瘤产生的 IgA 仍然保留了细菌抗原结合能力，这意味着可能有一类新的治疗性抗体。针对特定物种的 IgA 具有一定的菌株特异性。鉴于每个人肠道中发现的独特细菌物种和菌株组成，我们的研究结果表明，IgA 抗体库是专门为结合“自身”肠道细菌而形成的。
